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Pit Vipers, Fat Lips and Personalized Medicine Nancy J. Brown, MD Funding: HL079184, HL065193 Consulting: Merck, Novartis, Forest, Via Investigation drug:

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Presentation on theme: "Pit Vipers, Fat Lips and Personalized Medicine Nancy J. Brown, MD Funding: HL079184, HL065193 Consulting: Merck, Novartis, Forest, Via Investigation drug:"— Presentation transcript:

1 Pit Vipers, Fat Lips and Personalized Medicine Nancy J. Brown, MD Funding: HL079184, HL Consulting: Merck, Novartis, Forest, Via Investigation drug: icatibant

2 Drugs that interrupt the renin-angiotensin- aldosterone system save lives DRI X ARB X X MR antag X

3 Risk of ACE inhibitor-associated angioedema is increased in black Americans Events (n)Rate/10 3 Risk RatioP Race Black White ( ) 1 < Brown Clin Pharmacol Ther 1996 Utilized Tennessee Medicaid database Confirmed cases by chart review Compared rates of angioedema blacks and whites taking ACE inhibitors Normalized to rates in patients taking a calcium channel blocker

4 Mechanism(s) of ACE inhibitor-associated angioedema

5 Negative surface KK C1INH Activation of the intrinsic coagulation pathway KHPM pKK KK FXII FXIIa KHPM FXI FXIa Bradykinin Arg 1 Pro 7 Ser 6 Phe 5 Gly 4 Pro 3 Pro 2 Phe 8 C Arg 9 Arg 1 Pro 7 Ser 6 Phe 5 Gly 4 Pro 3 Pro 2 Phe 8 C Des Arg 9 -BK Arg 1 Phe 7 Gln 6 Gln 5 Pro 4 Lys 3 Pro 2 Phe 8 C Gly 9 Leu 10 Met 11 Substance P APPACECPN NEPDPPIV

6 DPPIV deficiency increases susceptibility to ACE inhibitor-induced peritracheal edema Byrd et al J Allergy Clin Immunol 2008

7 DPPIV inhibitor use is associated with increased risk of ACEi angioedema Brown et al Hypertension 2009

8 A Healthy Tension Personalized Medicine Evidenced-based Medicine Comparative Efficacy Blockbuster Drugs from Monty Python

9 Thank you Libby Stone, RN Alencia Woodard-Grice, PhD Brian Byrd, MDAnnis Marney, MD Albert Adam, PhD University of Montreal Marie Griffin, MD Wayne Ray, PhD Division of Pharmacoepidemiology


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